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Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood.

Svobodova T, Mejstrikova E, Salzer U, Sukova M, Hubacek P, Matej R, Vasakova M, Hornofova L, Dvorakova M, Fronkova E, Votava F, Freiberger T, Pohunek P, Stary J, Janda A - BMC Pulm Med (2015)

Bottom Line: Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C).The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient.A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. tamara.svobodova@lfmotol.cuni.cz.

ABSTRACT

Background: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease.

Case presentation: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient's pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient's brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen.

Conclusion: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient's family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

No MeSH data available.


Related in: MedlinePlus

Pulmonary changes in the index patient. A: Diffuse bilateral linear and reticular opacities, compatible with interstitial pulmonary involvement (chest X-ray). B: Diffuse subpleural fibrotic changes – honeycomb (black asterisk), areas of subpleural consolidations (blue asterisk) and bronchectasis (red asterisk) in the upper lobes (high-resolution computer tomography scan). C: Chronic reparative and resorptive reaction: fibrosis and cystic rearrangement (green arrows) and cholesterol clefts (blue arrows) in the upper left lobe (hematoxylin and eosin tissue stain; original magnification 50x). D: Thickened arterial wall, destruction of the elastic layer, thrombosis showing organizing vasculitis (red arrows) in the upper left lobe (elastin tissue stain; original magnification 250x).
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Fig1: Pulmonary changes in the index patient. A: Diffuse bilateral linear and reticular opacities, compatible with interstitial pulmonary involvement (chest X-ray). B: Diffuse subpleural fibrotic changes – honeycomb (black asterisk), areas of subpleural consolidations (blue asterisk) and bronchectasis (red asterisk) in the upper lobes (high-resolution computer tomography scan). C: Chronic reparative and resorptive reaction: fibrosis and cystic rearrangement (green arrows) and cholesterol clefts (blue arrows) in the upper left lobe (hematoxylin and eosin tissue stain; original magnification 50x). D: Thickened arterial wall, destruction of the elastic layer, thrombosis showing organizing vasculitis (red arrows) in the upper left lobe (elastin tissue stain; original magnification 250x).

Mentions: A 17-year-old Caucasian male presented to the hospital with acute fever, malaise, headache, cough and dyspnea. A bilateral pneumonia with signs of systemic inflammation corresponding to bacterial infection (C-reactive protein 210 mg/l) was diagnosed and antibiotic treatment initiated. No causative microorganism was identified. Despite rapid clinical improvement, chest X-ray showed persistent interstitial changes (Figure 1A). A subsequent high-resolution computer tomography (HRCT) revealed marked lung damage suggestive of bronchiectasis with peribronchitis, fibrotisation, subpleural cystic remodeling (honey-combing) and emphysema (Figure 1B). Interestingly, pulmonary function tests showed normal vital capacity, total lung capacity as well as diffusing capacity (Table 1). Thus, we detected chronic lung changes with no functional correlate during the first episode of pneumonia in a previously healthy boy. Further investigations to unfold the cause for the diffuse parenchymal lung disease were initiated.Figure 1


Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood.

Svobodova T, Mejstrikova E, Salzer U, Sukova M, Hubacek P, Matej R, Vasakova M, Hornofova L, Dvorakova M, Fronkova E, Votava F, Freiberger T, Pohunek P, Stary J, Janda A - BMC Pulm Med (2015)

Pulmonary changes in the index patient. A: Diffuse bilateral linear and reticular opacities, compatible with interstitial pulmonary involvement (chest X-ray). B: Diffuse subpleural fibrotic changes – honeycomb (black asterisk), areas of subpleural consolidations (blue asterisk) and bronchectasis (red asterisk) in the upper lobes (high-resolution computer tomography scan). C: Chronic reparative and resorptive reaction: fibrosis and cystic rearrangement (green arrows) and cholesterol clefts (blue arrows) in the upper left lobe (hematoxylin and eosin tissue stain; original magnification 50x). D: Thickened arterial wall, destruction of the elastic layer, thrombosis showing organizing vasculitis (red arrows) in the upper left lobe (elastin tissue stain; original magnification 250x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340788&req=5

Fig1: Pulmonary changes in the index patient. A: Diffuse bilateral linear and reticular opacities, compatible with interstitial pulmonary involvement (chest X-ray). B: Diffuse subpleural fibrotic changes – honeycomb (black asterisk), areas of subpleural consolidations (blue asterisk) and bronchectasis (red asterisk) in the upper lobes (high-resolution computer tomography scan). C: Chronic reparative and resorptive reaction: fibrosis and cystic rearrangement (green arrows) and cholesterol clefts (blue arrows) in the upper left lobe (hematoxylin and eosin tissue stain; original magnification 50x). D: Thickened arterial wall, destruction of the elastic layer, thrombosis showing organizing vasculitis (red arrows) in the upper left lobe (elastin tissue stain; original magnification 250x).
Mentions: A 17-year-old Caucasian male presented to the hospital with acute fever, malaise, headache, cough and dyspnea. A bilateral pneumonia with signs of systemic inflammation corresponding to bacterial infection (C-reactive protein 210 mg/l) was diagnosed and antibiotic treatment initiated. No causative microorganism was identified. Despite rapid clinical improvement, chest X-ray showed persistent interstitial changes (Figure 1A). A subsequent high-resolution computer tomography (HRCT) revealed marked lung damage suggestive of bronchiectasis with peribronchitis, fibrotisation, subpleural cystic remodeling (honey-combing) and emphysema (Figure 1B). Interestingly, pulmonary function tests showed normal vital capacity, total lung capacity as well as diffusing capacity (Table 1). Thus, we detected chronic lung changes with no functional correlate during the first episode of pneumonia in a previously healthy boy. Further investigations to unfold the cause for the diffuse parenchymal lung disease were initiated.Figure 1

Bottom Line: Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C).The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient.A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. tamara.svobodova@lfmotol.cuni.cz.

ABSTRACT

Background: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease.

Case presentation: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient's pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient's brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen.

Conclusion: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient's family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

No MeSH data available.


Related in: MedlinePlus